The European Commission approved the use of Keytruda (pembrolizumab), in combination with Alimta (pemetrexed) and platinum-based chemotherapy, as a first-line treatment for metastatic nonsquamous non-small cell lung cancer (NSCLC).
The approval is for patients who have no EGFR or ALK mutations in their tumors, and was based on promising overall survival and progression-free survival data from the Phase 3 KEYNOTE-189 trial (NCT02578680). Keytruda, by Merck (known as MSD outside the U.S. and Canada), is now the first PD-1 inhibitor approved in Europe for use with chemotherapy.
“We are very pleased that the European Commission has approved Keytruda in combination with chemotherapy based on the significant survival benefit demonstrated in the KEYNOTE-189 trial,” Roger M. Perlmutter, president of Merck Research Laboratories, said in a press release. “This approval is a first in Europe and adds to the rapidly growing role of Keytruda as a foundation for the treatment of lung cancer.”
The Phase 3 KEYNOTE-189 trial compared the effectiveness and safety of Alimta and platinum-based chemotherapy — Platinol (cisplatin) or Paraplatin (carboplatin) — combined with Keytruda or placebo in patients with nonsquamous NSCLC with any level of PD-L1 expression.
Patients had not received any prior therapy for their metastatic disease and had no mutations in the EGFR or ALK genes. They received treatment for a maximum of two years, or until they experienced signs of disease progression or toxicity. Patients in the placebo arm were allowed to move to Keytruda if their disease worsened.
The study’s main goal was to determine if Keytruda’s inclusion extended overall survival and progression-free survival – the length of time a patient lives without disease worsening – as determined by radiologic review. Secondary measures included overall response rate, duration of response, and safety.
Compared to chemotherapy alone, data showed that the addition of Keytruda reduced the risk of death by 51% and the risk of disease progression or death by 48%. Keytruda also improved response rates – 48% vs. 19% – and the time a patient kept responding to treatment – 11.2 months vs. 7.8 months.
Patients across all PD-L1 categories demonstrated an improvement in overall survival, indicating a benefit for all patients.
The combo treatment’s safety was examined using data from KEYNOTE-189 and another trial testing the combination in a similar patient population – KEYNOTE-021 (NCT02039674).
Among the 488 patients studied, nausea was the most frequent adverse event (47%), followed by anemia, fatigue, low neutrophil levels, and loss of appetite. Severe to life-threatening adverse reactions were more common among those taking Keytruda (47%) compared to the chemotherapy group (37%).
KEYNOTE-189 was part of a collaboration between Merck and Alimta’s maker, Eli Lilly and Company. With the approval, Keytruda can now be marketed in all 28 European Union member states plus Iceland, Lichtenstein, and Norway.
The medicine is also approved in Europe as a first-line treatment of metastatic squamous or nonsquamous NSCLC patients with high PD-L1 levels and no EGFR or ALK mutations, and for advanced NSCLC patients with PD-L1-positive tumors who received at least of prior line of chemotherapy. But for these indications, Keytruda is used as a single agent.
“Lung cancer is the leading cause of cancer death in Europe, and we are committed to doing everything in our power to help address it,” said Frank Clyburn, president of Merck Oncology. “Today Keytruda is now approved across Europe for the treatment of appropriate patients with metastatic nonsquamous non-small cell lung cancer as both a monotherapy and in combination with chemotherapy.”
The PD-1 receptor on immune cells usually acts as an “off switch,” keeping them from being overly active and attacking a person’s own tissues and cells. But tumor cells can take advantage of this mechanism, producing large amounts of the PD-L1 ligand, which helps them evade immune surveillance.
Keytruda is an immune checkpoint inhibitor designed to prevent this from happening, restoring the immune system’s ability to mount an attack against tumor cells.